Methanol → 6-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinic acid

HRID 882262Notes

Reaction equation

HRID 882262 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:23]=[CH:22][C:17]([C:18]([O:20]C)=[O:19])=[CH:16][N:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:6][C@@H:5]1[CH3:32])(=[O:3])[CH3:2].O.[OH-].[Li+].CO>O>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:23]=[CH:22][C:17]([C:18]([OH:20])=[O:19])=[CH:16][N:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:6][C@@H:5]1[CH3:32])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 168937Lithium hydroxide, monohydrateHCID 86709428methyl 6-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinate2×

Product 1

HCID 867094306-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinic acidYield 97.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a stirring solution of crude methyl 6-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinate (Intermediate 62) (2.2 g, 5.01 mmol) in MeOHl (12 mL), was added lithium hydroxide monohydrate (0.144 g, 6.01 mmol) in water (12 mL) and the mixture warmed to 50° C. for 70 mins. MeOH (10 mL) was added and the mixture stirred at 50° C. for a further 50 mins. The mixture was allowed to cool to room temperature before being partitioned between saturated aqueous sodium bicarbonate (150 mL) and DCM (3×150 mL). The aqueous layer was then treated with 2M HCl until acidic (˜pH 3) before being extracted with DCM (3×150 ml). The organics were combined, dried by passing through a hydrophobic frit and concentrated in vacuo to give 6-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinic acid (2.08 g, 4.89 mmol). LCMS: (Formate, 2 min), Rt=0.86 mins, MH+426.

Workup

  1. temperatureto cool to room temperature
  2. custombefore being partitioned between saturated aqueous sodium bicarbonate (150 mL) and DCM (3×150 mL)
  3. additionThe aqueous layer was then treated with 2M HCl until acidic (˜pH 3)
  4. extractionbefore being extracted with DCM (3×150 ml)
  5. customdried
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-27d2885b2ad24580a5d7ede03172f545
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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